Field of the Invention
This invention relates to a process for fabricating artificial blood vessels that may be grafted as a substitute or to replace a portion of a human blood vessel. More specifically it relates to an artificial blood vessel that approaches the properties of a human blood vessel in its various properties such as pulsatility, elasticity, compatibility to blood, compliance, permeability, etc. (Pulsatility is the ability of a blood vessel to develop sufficient pressure to cause blood to flow therethrough--too much permeability will allow blood flow through the pores and thereby hinder build-up of sufficient pressure to allow blood flow through the blood vessel. Elasticity in radial and longitudinal directions impart good pulsatility and compliance. Compatibility to blood relates to surface properties of the blood vessel--thus a more inactive surface means the blood vessel is more blood compatible whereas a more reactive surface means the surface interacts with the blood.) Still more specifically it relates to an artificial blood vessel and method for producing the same with controlled permeability to allow the passage of nutrients, ions, and other body fluid in a manner similar to that permitted by human blood vessels. Once this passage of ions, etc., is permitted by the artificial blood vessels, this acts as a precursor to the entire healing process and in return the graft remains open or patent for extended periods.
The following patents exemplify the prior art.
U.S. Pat. No. 3,562,352 describes block copolymers of either polyether urethanes or polyester urethanes and polysiloxanes, preferably poly(dimethylsiloxane). Example 11 describes the preparation of a tube having both inner and outer surfaces of the block copolymer of a polyether urethane--poly(dimethylsiloxane) from a solution in which the solvent is a combination of 1000 parts by weight of tetrahydrofuran per 1200 parts by weight of dioxane. "A precleaned, highly polished stainless steel mandril was dipped into solution and allowed to partially dry. While in a semidry condition, the tube while still on the mandril was wrapped with one layer of a number 20 Dacron mesh fabric presoaked in purified anhydrous tetrahydrofuran. The Dacron wrapped tube was then dipped into the block-copolymer solution to deposit an additional layer over the Dacron fabric. The tube while still on the mandril was allowed to dry completely at room temperature and subsequently maintained at 80.degree. C. for one to two hours. It was removed from the mandril. Final dimensions of the tube are 1.8 cm. inside diameter, 12.5 cm. length and 0.03 cm. wall thickness." It is described as suitable, with appropriate sterilization, for use as a saturable aortic graft.
Sawyer U.S. Pat. No. 4,167,045 shows the production of cardiac and vascular prostheses which comprises a Dacron crimped vascular graft coated with protein applied from a protein solution. These were further modified by the addition of ground solid succinic anhydride. The grafts were hydrostatically tested to withstand 30 mm of Hg pressure "without showing evidence of air leaks through the graft pores" (Col. 7, lines 43-45). These grafts were also tested with various deposited powders, such as Agar, aluminum, etc. There is no indication of a control of or desired range of permeability.
U.S. Pat. No. 4,623,347 teaches the prevention of clotting of blood in contact with antithrombogenic elastomers prepared by mixing solutions of polyurethane and polysiloxane having reactive terminal groups and reacting them to produce a molded product therefrom. Films of such products were cast on the surface of a test tube. Patentee indicates that similar castings or molding may be used to cover the exposed surfaces of medical devices and instruments which come into direct contact with blood.
Nyilas U.S. Pat. No. 4,670,286 describes a vascular prosthesis of a bioresorbable material (polyglycolic acid) intertwined with nonresorbable (Dacron). The bioresorbable materials "become degraded and ultimately vanish, gradually increasing the biological porosity of the graft over its initial porosity." (Col. 4, lines 27-30). This involves a bioresorbable material which degrades and disappears so that after implantation shows an increase in porosity regardless of what it might have been originally. There is no disclosure of a controlled, desired low-initial permeability.
U.S. Pat. No. 4,675,361 also teaches polymer systems suitable for blood-contacting surfaces of a biomedical device. These systems comprise a base polymer, preferably a polyurethane, mixed with a block copolymer of polyurethane and polysiloxane. Example 4 describes a typical procedure using a solution of 99.0 weight percent of polyesterurethane and 0.1 weight percent silicone/polyurethane block copolymer in a solvent comprising 90% by volume of tetrahydrofurane and 10% dimethylformamide. This "solution is coated onto tapered stainless steel mandrels by multiple dipping. The solvent is allowed to evaporate and the film is removed from the mandrel. The resulting `balloon` is mounted on a predrilled catheter and is useful as a cardiac arrest device when placed in the descending aorta and inflated and deflated with CO.sub.2 in counterpulsation to the heart."
U.S. Pat. No. 4,685,280 describes an artificial vascular graft made of fibers in which the inner surface is made of fibers of less than 0.5 denier and the outer surface is made of fibers of more than 1.0 denier. Polymers specified are polyamides, polyurethanes, polyolefins and preferably polyesters. Other fibers may be mixed with these which are of a type such as polystyrene which may be removed or stripped, for example, by a solvent. This patent states in col. 3, lines 37-52:
"It is convenient to refer to the rate of water permeation as a standard measure. The phrase rate of water permeation, is defined here as the amount (ml/minute) of water permeating through 1 cm.sup.2 of the surface of the grafts (or cloth) under 120 mm Hg of pressure.
To prevent blood leakage, this rate should be below 500 ml/min, and preferably below 100 ml/min. These values are only guides and it is unnecessary to adhere to them strictly. There may be many cases where artificial vascular grafts of this invention have rates of water permeation of 3000 and 5000 ml/min but are superior to conventional artificial vascular grafts in formation of intervascular endothelium and in utility for anastomosis. But performance of the artificial vascular grafts is particularly good when the rate of water permeation is low."
U.S. Pat. No. 4,731,073 shows an arterial graft prosthesis formed of a core zone of porous elastomer disposed about the longitudinal axis of the prosthesis, an inner zone of solid elastomer joined to the inner surface of the zone of porous elastomer, and an outer zone of solid elastomer, this outer zone of solid elastomer being joined to the outside of the zone of porous elastomer. There is little information as to the polymer compositions of the various layers although some zones are identified as polyether-polyurethane "having a lack of pores or orifices".
Pinchuk U.S. Pat. No. 4,851,009 shows the treatment of prostheses made of fibers of polyurethane, polypropylene and polymethacrylate with a silicone rubber to reduce or prevent surface fissuring or cracking and shows plasma pretreatment for grafting silicone polymers onto the substrate. The polyester of the present invention does not exhibit either surface fissuring or cracking.
Kira U.S. Pat. No. 4,871,361 describes an artificial blood vessel comprising two concentric layers made of an elastomer, the inner layer having a porosity of 80-95% and the other layer(s) having a lower porosity so that the overall porosity is 75-90%. This range of porosity is well above the permeability range of applicant's product, as described hereinafter, and will require blood preclotting to bring the product within the desired low permeability range, which preclotting is not necessary with applicant's product of the present invention. Moreover, Kiro's method of producing pores in his product is entirely different from applicant's. Kiro does not apply any coating but instead has a soluble substituent in his base material which, upon treatment with an appropriate solvent, is removed to leave openings or pores. Kiro does not aim for or teach a low porosity and if the soluble substituent is not completely removed by solvent treatment, this substituent will be leached out by the blood thereby eventually producing even higher porosity.
Fleckenstein et al disclose porous artificial blood vessels comprising polyethylene terephthalate fibers which have been impregnated with gelatin which is subsequently crosslinked with a diisocyanate. The gelatin, as well as collagen, albumin, etc., used as impregnants, all invoke immune responses in the body. Each of these materials is intended to degrade in the human body but in reality they do not degrade. Moreover coatings with biologic materials tend to flake off during or after implantation which is not the case with applicant's fabricated products.
None of these patents teach applicant's method of controlling or adjusting the permeability of an artificial vascular graft.
Permeability is an important property in facilitating the transmission of appropriate ions in body fluids passing into and out of the vascular system.
For general replacement of blood vessels it is desirable to have artificial blood vessels available with inside diameters ranging from 1 mm. to 34 mm. At present artificial blood vessels are available only with inside diameters of 8 mm. or greater. With tubes smaller than 8 mm. I.D. there are a number of problems which include high permeability leading to blood clotting, occlusion, etc. It is desirable therefore to be able to have artificial blood vessels in the full range including less than 8 mm. I.D. which have low, controlled optimum permeability which will avoid or minimize blood occlusion and clotting.